Since the discovery of nerve growth factor (NGF) by Levi-Monntalcini (Annual New York Academy of Science, 55, 330 (1952)) and Cohen et al. (Proceedings of National Academy of Science, USA, 40, 1014 (1954)), a large number of neurotrophic factors have been found. These factors are believed to play various roles such as nerve cell differentiation, maturation, survival, homeostasis and proliferation. In addition to the above-mentioned NGF, these factors include brain-derived neurotrophic factor (BDNF) (Barde Y-A et al., EMBO J. 1, 549-553 (1982)) and ciliary neurotrophic factor (CNTF) (Watters, D. et al, J. Neurochem., 49, 705-713 (1987)). Neurotrophic activity is also found in fibroblast growth factors (FGFS), epidermal growth factor (EGF), insulin-like growth factor (IGF) and interleukin-6 (IL-6).
As a factor showing high homology to NGF, human nerve growth factor 2 was discovered by Kaisho et al. (European Patent Publication No. 386,752; FEBS Letters, 266, 187-191 (1990)).
The same factor has been reported in other publications (e.g., Hohn et al., Nature, 344, 399 (1990)).
In the present specification, human nerve growth factor 2 is also referred to as human NGF2/NT-8. With respect to its human NGF2/NT-3, while much remains unknown as to action and structure, the following is known: (1) The human NGF2/NT-3 gene is highly expressed in the human hippocampus and cerebellum. (2) The degree of expression is higher in newborns than mature animals (rats). (3) It acts on nerve cells on which NGF or BDNF has no or weak action, such as nodose ganglion derived nerve cells. These findings suggest that human NGF2/NT-3 plays a key role in nervous system development.
Production of human NGF2/NT-3 in large amounts will help to further elucidate its bioactivities, which in turn, will facilitate commercial production thereof.